Double-stranded RNA molecules (dsRNA) have been shown to modulate gene expression in a highly conserved mechanism known as RNA interference (RNAi). This mechanism has now become the focus for the development of a new class of pharmaceutical agents for treating disorders that are caused by the aberrant or unwanted regulation of a gene.
Given the focus in the art surrounding delivery of RNAi therapeutics, effective delivery of therapeutic compounds to a target organ or system is often the largest hurdle facing a potentially lifesaving treatment. And while certain methods of formulating therapeutics in lipid particles and liposomes are known in the art, for example those described in U.S. Pat. Nos. 7,901,708; 7,811,603; 7,030,097; 6,858,224; 6,106,858; 5,478,860 and 5,908,777, the contents of which are each incorporated herein by reference, there remains a need for improved processes and apparatuses for the manufacture of lipid nanoparticles capable of carrying a therapeutic payload. The present invention provides such methods, processes and systems for the manufacture of lipid nanoparticles which sufficiently encapsulate a nucleic acid payload, specifically RNAi agents, for delivery to mammalian cells.